The long-term goal of this project is to understand at the molecular level how interactions between retroviral envelope (Env) proteins and cellular receptors lead to viral entry. The proposed studies will significantly advance our understanding of retroviral entry using the Avian Sarcoma and Leukosis Virus (ASLV) as a model system. Specifically, these studies will lead to the identification of the receptor-binding determinants of ASLV-B and will generate various forms of ASLV-B Env that are competent for receptor-binding for use in future crystallization trials. In particular, characterization of the stable receptor-primed intermediate of ASLV-B Env promises to shed new insight into how a retroviral Env protein is converted from its native state to a fusion-active state. Taken together these studies will enhance our understanding of the entry mechanisms used by retroviruses as well as by other viruses, such as influenza and Ebola which have similar types of envelope proteins.